Daporinad

Daporinad
Clinical data
Drug classNAMPT inhibitor
Identifiers
  • (E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-pyridin-3-ylprop-2-enamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.316.982
Chemical and physical data
FormulaC24H29N3O2
Molar mass391.515 g·mol−1
3D model (JSmol)
  • C1CN(CCC1CCCCNC(=O)/C=C/C2=CN=CC=C2)C(=O)C3=CC=CC=C3
  • InChI=1S/C24H29N3O2/c28-23(12-11-21-8-6-15-25-19-21)26-16-5-4-7-20-13-17-27(18-14-20)24(29)22-9-2-1-3-10-22/h1-3,6,8-12,15,19-20H,4-5,7,13-14,16-18H2,(H,26,28)/b12-11+
  • Key:KPBNHDGDUADAGP-VAWYXSNFSA-N

Daporinad (FK866, APO866), is a drug which acts as a selective inhibitor of the enzyme nicotinamide phosphoribosyltransferase (NAMPT). Levels of this enzyme are elevated in certain forms of cancer such as leukemia, and it was hoped that NAMPT inhibitors would be useful in the treatment of cancer. Unfortunately, dapinorad was unsuccessful in clinical trials due to lack of efficacy, but it still has antiinflammatory effects and may be useful for other medical applications such as arthritis, as well as being widely used as a tool compound for the study of NAMPT and its function.[1][2][3][4][5][6][7]

Daporinad was originally identified and developed by Klinge Pharma G.m.b.H.,[8] Development rights then moved through a corporate chain in which Fujisawa Deutschland GmbH[9] which later merged into Astellas held APO866/FK866 and subsequently out-licensed the worldwide development and marketing rights to the Danish oncology company TopoTarget in 2005, after which TopoTarget merged with BioAlliance Pharma to form Onxeo, which later rebranded as Valerio Therapeutics.[10]

References

  1. ^ Bi TQ, Che XM (July 2010). "Nampt/PBEF/visfatin and cancer". Cancer Biology & Therapy. 10 (2): 119–125. doi:10.4161/cbt.10.2.12581. PMID 20647743.
  2. ^ Montecucco F, Cea M, Cagnetta A, Damonte P, Nahimana A, Ballestrero A, et al. (2013). "Nicotinamide phosphoribosyltransferase as a target in inflammation- related disorders". Current Topics in Medicinal Chemistry. 13 (23): 2930–2938. doi:10.2174/15680266113136660208. PMID 24171767.
  3. ^ Galli U, Travelli C, Massarotti A, Fakhfouri G, Rahimian R, Tron GC, et al. (August 2013). "Medicinal chemistry of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors". Journal of Medicinal Chemistry. 56 (16): 6279–6296. doi:10.1021/jm4001049. PMID 23679915.
  4. ^ Franco-Trepat E, Alonso-Pérez A, Guillán-Fresco M, Jorge-Mora A, Gualillo O, Gómez-Reino JJ, et al. (July 2019). "Visfatin as a therapeutic target for rheumatoid arthritis". Expert Opinion on Therapeutic Targets. 23 (7): 607–618. doi:10.1080/14728222.2019.1617274. PMID 31074669.
  5. ^ Ghanem MS, Monacelli F, Nencioni A (May 2021). "Advances in NAD-Lowering Agents for Cancer Treatment". Nutrients. 13 (5): 1665. doi:10.3390/nu13051665. PMC 8156468. PMID 34068917.
  6. ^ Wei Y, Xiang H, Zhang W (2022). "Review of various NAMPT inhibitors for the treatment of cancer". Frontiers in Pharmacology. 13 970553. doi:10.3389/fphar.2022.970553. PMC 9490061. PMID 36160449.
  7. ^ Mylonakis A, Kozadinos A, Frountzas M, Kapetanakis EI, Lidoriki I, Despotidis M, et al. (April 2025). "The Role of Visfatin in Gastric and Esophageal Cancer: From Biomarker to Therapeutic Target". Cancers. 17 (8): 1377. doi:10.3390/cancers17081377. PMC 12025392. PMID 40282553.
  8. ^ WO 1997/048696A1, Biedermann E, Hasmann M, Löser R, Rattel B, Reiter F, Schein B, Seibel K, Vogt K, "Pyridyl alkene- and pyridyl alkyne-acid amides as cytostatics and immunosuppressives", published 1997-12-24, assigned to Klinge Pharma GmbH  Example 7: N-[4-(l-benzoylpiperidin-4-yl)-butyl]-3-(pyridin-3-yl)-acrylamide (substance 159)
  9. ^ Hasmann M, Schemainda I (November 2003). "FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis". Cancer Research. 63 (21): 7436–7442. PMID 14612543.
  10. ^ "Valerio Therapeutics SA". Synapse. PatSnap.
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